Abstract / Description of output
Chronically elevated glucocorticoid levels cause obesity, diabetes, heart disease, mood disorders and memory impairments. 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) catalyses intracellular regeneration of active glucocorticoids (cortisol, corticosterone) from inert 11 -keto forms in liver, adipose and brain, amplifying local action. Obese humans and rodents show increased I I beta-HSD I in adipose tissue. Transgenic mice overexpressing 11 beta-HSDI selectively in adipose tissue faithfully recapitulate metabolic syndrome. Conversely, 11 beta-HSD I knockout mice have a 'cardioprotective' phenotype, whose effects are also seen with I 1 beta-HSD1 inhibitors in rodents. However, any major metabolic effects of 11 beta-HSD1 inhibition in humans are, as yet, unreported. 1 1 beta-HSD 1 null mice also resist congitive decline with ageing, and this is seen in humans with a prototypic inhibitor. Thus 11 beta-HSD1 inhibition is an emerging pleiotropic therapeutic target.
Original language | English |
---|---|
Pages (from-to) | 504-520 |
Number of pages | 17 |
Journal | Drug Discovery Today |
Volume | 12 |
Issue number | 13-14 |
Publication status | Published - Jul 2007 |
Keywords / Materials (for Non-textual outputs)
- CORTISONE REDUCTASE DEFICIENCY
- HEPATIC INSULIN SENSITIVITY
- OBESE ZUCKER RATS
- ENCODING 11-BETA-HYDROXYSTEROID DEHYDROGENASE
- POLYCYSTIC-OVARY-SYNDROME
- PITUITARY-ADRENAL AXIS
- HUMAN ADIPOSE-TISSUE
- HEXOSE-6-PHOSPHATE DEHYDROGENASE
- IN-VIVO
- ENDOPLASMIC-RETICULUM